TRANSPLACENTAL PRIMING OF THE HUMAN IMMUNE SYSTEM TO ENVIRONMENTAL ALLERGENS - UNIVERSAL SKEWING OF INITIAL T-CELL RESPONSES TOWARD THE TH2CYTOKINE PROFILE

The expression of Th2-skewed immunity against soluble protein Ags pres ent in the normal environment is recognized as the primary cause of al lergic inflammation in atopics, In contrast, nonallergic normal indivi duals display low level Th1-skewed immunity against the same Ags (''al lergens''), which is perceived as conferring protection against Th2-de pendent allergic sensitization. The type of T cell memory that develop s against these Ags is currently believed to be the result of complex interactions between environmental and genetic susceptibility factors, which occur postnatally when the naive immune system directly confron ts the outside environment. The results of the present study challenge this general concept. We demonstrate here for the first time that Th2 -skewed responses to common environmental allergens, comprising IL-4, IL-5, IL-6, IL-9, and IL-13, are present in virtually all newborn infa nts and are dominated by high level production of IL-10, Moreover, the se responses are demonstrable within 24 h of culture initiation, argui ng against a significant contribution from covert in vitro T cell prim ing and/or differentiation. These findings imply that the key etiologi c factor in atopic disease may not be the initial acquisition of aller gen-specific Th2-skewed immunity per se, but instead may be the effici ency of immune deviation mechanisms, which in normal (nonatopic) indiv iduals redirect these fetal immune responses toward the Th1 cytokine p henotype.